Genetic variations of the dihydrofolate reductase gene of Plasmodium vivax in Mandalay Division, Myanmar

Na, Byoung Kuk; Lee, Hyeong Woo; Moon, Seung‐Hyeon; In, Tae Suk; Lin, Khin; Maung, Maung; Chung, Gyung Tae; Lee, Jong Koo; Kim, Tong Soo; Kong, Yoon

doi:10.1007/s00436-005-1364-0

Cited by 30 publications

(29 citation statements)

References 26 publications

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“…Because this mutation occurs at a high frequency (9.1%), the characteristics of this residue warrant further study. Regarding the combinations of mutations in pvdhfr , the observations that mutation 117N was not observed in the pvdhfr quadruple mutants in this study, although the quadruple mutants always included the mutation 117N/T in previous studies, 5,11 and that mutation 61M was only seen in the quadruple mutants, are consistent with previous data. 26 However, the observation that 57L was not linked to 58R, but occurred alone in a small percentage of isolates from Korea (22.7%), is inconsistent with the results of a previous study.…”

Section: Discussionsupporting

confidence: 92%

“…22 However, in 1999 (this study), 7 of 14 isolates were double mutants, 3 of 14 isolates were quadruple mutants, and 3 isolates carried only wild-type alleles; there were no triple mutants. In contrast, in 2005, 9 of 21 isolates were double mutants and 8 were quadruple mutants, 11 which indicated that these mutations may increase rapidly in isolates with highly mutated pvdhfr alleles. Therefore, the thorough and frequent surveillance of SNPs of drug-resistance genes is useful and important in monitoring drug resistance in malaria-endemic countries.…”

Section: Discussionmentioning

confidence: 96%

“…7 Several previous reports are also available regarding the current status of drug-resistant P. vivax malaria in Myanmar. [8][9][10][11] Since 1953, P. vivax malaria has reemerged in the Republic of Korea, and CQ/primaquine has been used for the treatment of these patients with P. vivax malaria. 12 Sulfadoximepyrimethamine resistance in P. falciparum is well established because of selection for point mutations in the dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) genes.…”

Section: Introductionmentioning

confidence: 99%

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Mutations in the Antifolate-Resistance-Associated Genes Dihydrofolate Reductase and Dihydropteroate Synthase in Plasmodium vivax Isolates from Malaria-Endemic Countries

Lim²,

Nam³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Plasmodium vivax -infected blood samples. Blood samples obtained from patients with P. vivax infections at local hospitals in malaria-endemic areas of Korea (n = 97) during [2007][2008][2009]. Samples from Thailand (n = 30) were obtained from malaria patients who were admitted to a local health center in Mae Sod, Thailand, during 2008, and Abstract. Parasite dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) are known target enzymes of antifolate drugs used for the treatment and prophylaxis of persons with malaria. We sequenced the Plasmodium vivax dihydrofolate reductase ( pvdhfr ) and dihydropteroate synthase ( pvdhps ) genes to examine the prevalence and extent of point mutations in isolates from malaria-endemic countries. Double mutations (S58R and S117N) or quadruple mutations (F57L/I, S58R, T61M, and S117T) in the pvdhfr gene were found in isolates from Thailand (96.4%) and Myanmar (71.4%), but in only one isolate (1.0%) from Korea, where sulfadoxine-pyrimethamine has never been used. The pvdhfr point mutations correlated strongly with the pvdhps point mutations and ranged from single to triple mutations (S382A, A383G, and A553G), among isolates from Thailand, Myanmar, and Korea. These findings suggests that the prevalence of mutations in pvdhfr and pvdhps in P. vivax isolates from different malaria-endemic countries is associated with selection pressure imposed by sulfadoxine-pyrimethamine. DNA isolation. Genomic DNA was extracted from the whole blood samples by using a QIAamp DNA Blood Kit (Qiagen, Valencia, CA), according to the manufacturer's instructions and from blood filter papers by using described methods. 17Sequencing of pvdhfr and pvdhps genes . The pvdhfr (GenBank accession no. X98123) and pvdhps (AY186730) gene sequences used as the reference wild type were amplified by polymerase chain reaction (PCR) using gene-specific primers. Amplifications were performed in a reaction mixture that contained 2 μL of 10 × buffer, 2.5 mM MgCl 2 , 0.2 mM of each dNTP, 0.25 μM of each primer, 0.5 U of AmpliTaq Gold DNA polymerase (Applied Biosystems, Foster City, CA), and 1 μL of genomic DNA or the amplicon from the first PCR. Primer Pvdhfr F1 (sense) 5′-ATGGAGGACCTTTCAGATGTATT-3′ and primer Pvdhfr R1 (antisense) 5′-CCACCTTGCTGTA AACCAAAAAGTCCAGAG-3′ (expected amplicon size = 715 basepairs, nucleotides 1-715) were used as primers for the first-round amplification of the pvdhfr gene. 18 The PCR was performed with an initial denaturation at 94°C for 10 minutes and 35 cycles at 94°C for 50 seconds, 58°C for 50 seconds, and 72°C for 50 seconds.Primer Pvdhfr F3 (sense) 5′-TTTGACATTTACGCCATC TGC-3′ and primer Pvdhfr R3 (antisense) 5′-TACACCTC ACTGACGGACG-3′ (expected amplicon size = 647 basepairs, nucleotides 22-668) were used for the second-round amplification of pvdhfr . The PCR cycling conditions for pvdhfr were an initial denaturation at 94°C for 10 minutes and 35 cycles at 94°C for 30 seconds, 60°C for 50 seconds, and 72°C for 1 minute.Primer Pvdhps F1 (sense) 5′-AGGAAGCCATTCGCTC AAC-3′ and pr...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Mutations in the Antifolate-Resistance-Associated Genes Dihydrofolate Reductase and Dihydropteroate Synthase in Plasmodium vivax Isolates from Malaria-Endemic Countries

Lim²,

Nam³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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“…The pvdhfr gene was amplified using the primer 5′-ATGGAGGACCTTTCAGATGTA TTTGACATT-3′ and 5′-CTTGCTGTAAACCAAAAAGTC CAGAGTGGT-3′ as described. 34 The PCR was performed with the following parameters: 94°C for 5 minutes; fol lowed by 30 cycles at 94°C for 20 seconds, 60°C for 30 seconds, and 72°C for 1 minute; and a final elongation at 72°C 10 minutes. The pvdhps gene was ampli fied by nested PCR with the outer primers (forward 5′-TTGAAACACGCATTATGGTATCG-3′ and reverse 5′-AAGCGTAGCGACAGAAGAACG-3′) and inner primers (forward 5′-GAGATTACCCTAAGGTTGAT GTATC-3′ and reverse 5′-GGTTTATTTGTCGATCCTGT G-3′).…”

Section: Samplementioning

confidence: 99%

Different Allele Prevalence in the Dihydrofolate Reductase and Dihydropteroate Synthase Genes in Plasmodium vivax Populations from China

Miao

Zhou

Cui

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Abstract. Antifolate resistance in Plasmodium vivax is caused by point mutations in genes encoding dihydrofolate reductase ( pvdhfr ) and dihydropteroate synthase ( pvdhps ). In this study, we used direct sequencing to survey pvdhfr and pvdhps mutations in 122 clinical P. vivax isolates from a central and a southern province of China. For pvdhfr , 36.9% were wild-type, whereas mutations were detected at four codons (57, 58, 61, and 117). The S117N/T mutation was the most prevalent (48.4%), followed by the T61M mutation (18.9%). Six pvdhfr mutant alleles were found, ranging from 37.7% to 0.8%. The dramatically different pvdhfr allele frequencies between the two P. vivax populations might be caused by different drug histories or intrinsic difference between temperate and subtropical strains. In contrast, except polymorphisms within a repeat region, no resistance-conferring mutations were detected in pvdhps . Our result suggests that P. vivax populations in China may be relatively susceptible to sulfadoxine-pyrimethamine.

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“…2017; 10(9):e57697. 5 resistance in P. falciparum, quadruple mutant alleles of pvdhfr at codons 57, 58, 61, and 117 were predominated in clinical isolates from India, Myanmar, Indonesia (28)(29)(30), and Thailand (31). It appears that in these countries, diversity in the frequency of mutant pvdhfr alleles is a sign of drug pressure by usage of anti-folates.…”

Section: Discussionmentioning

confidence: 99%

Mutational Analysis of Plasmodium vivax dhfr Gene Among Cases in South East of Iran

Rafee

Zaman²,

Mehravaran

et al. 2017

Jundishapur J Microbiol

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Genetic variations of the dihydrofolate reductase gene of Plasmodium vivax in Mandalay Division, Myanmar

Cited by 30 publications

References 26 publications

Mutations in the Antifolate-Resistance-Associated Genes Dihydrofolate Reductase and Dihydropteroate Synthase in Plasmodium vivax Isolates from Malaria-Endemic Countries

Mutations in the Antifolate-Resistance-Associated Genes Dihydrofolate Reductase and Dihydropteroate Synthase in Plasmodium vivax Isolates from Malaria-Endemic Countries

Different Allele Prevalence in the Dihydrofolate Reductase and Dihydropteroate Synthase Genes in Plasmodium vivax Populations from China

Mutational Analysis of Plasmodium vivax dhfr Gene Among Cases in South East of Iran

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